On Cancer: Wiping Out Epstein-Barr Virus Preserves Transplant Success

Lucas T., a patient, with Susan Prockop, who leads research into Epstein-Barr virus.

Memorial Sloan Kettering physician-scientists are investigating a novel way to wipe out a potentially devastating complication that commonly occurs in patients who have received a stem cell or organ transplant as part of their treatment. These transplants can weaken the immune system, allowing a dormant pathogen called Epstein-Barr virus (EBV) to awaken and trigger a new malignancy.

Epstein-Barr virus (EBV) is present in most people, but in those with a healthy immune system it may produce only mild symptoms or even go unnoticed. However, in someone whose immune system is not fully functional, EBV can cause infected cells to divide uncontrollably as a cancer in the lymph nodes, spleen, or even the liver, lungs, or brain. This can occur in both children and adults.

A Third-Party Remedy

The new approach involves giving these patients T cells (a type of immune cell) from a healthy third-party donor — someone not related to either the patient or any donor who previously gave blood or tissue to the patient. Once infused, the third-party T cells attack all EBV-infected cells, cancerous or not, and destroy them.

The third-party donors need to have been exposed at some point to EBV so their T cells recognize the virus. They also are matched with the recipient based on human leukocyteantigen (HLA) type. HLAs are proteins that vary between people and function as the “fingerprint” of an individual’s immune system. The HLA match need not be perfect but should be close enough that the donated T cells attack EBV effectively in the recipient’s cells.

The T cells from the third-party donor’s blood are cultured in the laboratory in a way that expands them to sufficient numbers to be therapeutic after infusion, a process that takes about two months.

Using a third-party donor — rather than the person who donated stem cells for the original transplant — can offer several advantages, Dr. Prockop explains. “Some stem cell or organ donors have never had EBV, so their T cells wouldn’t recognize the virus in the recipient effectively,” she says. “Also, the patient may develop the EBV malignancy before cells from these donors have been collected and expanded in the laboratory, and the patient can’t wait two months for this to occur. Finally, EBV malignancies can develop in non-transplant patients — their immune systems may be weakened from other causes.”

“Off-the-Shelf” Therapy

The researchers have now characterized more than 300 cell lines that are frozen and stored, meaning they are available as a kind of “off-the-shelf” resource when needed. This is essential in treating EBV malignancies, which tend to progress very rapidly.

Dr. Prockop says the third-party T cells have so far shown no undesirable side effects and the researchers are conducting a phase II clinical trial establishing the treatment’s long-term safety and effectiveness. The new approach has been used on 53 patients, both children and adults, and results have been promising. “We’re now being referred patients from all over the country to treat these EBV malignancies,” she says.

“These patients have absolutely no other recourse, so it is very striking to have such an effective therapy with no side effects,” she says.

Dr. Prockop adds that caring for patients allows her to see the clinical problem first-hand and drives home the urgency of finding a solution for patients who have already been through an ordeal and now have a terrible complication. “It’s the best version of oncology — the excitement of seeing our efforts make these children better while studying these EBV-directed T cells, trying to figure out how they work, why they work, and how we can make it better to help patients with no other options.”

Comments

Submitted by Berdj Joseph Rassam | Thursday, March 6, 2014 - 3:08 PM.

It's a wonderful goal to try and wipe out Epstein-Barr.

Submitted by James Trotto | Friday, March 7, 2014 - 1:27 PM.

Great hospital. Dr. Prockop along with her team provided the utmost care and concern for our son. Was always available to answer our questions and concerns regarding all treatment procedures. Keep up the great work!!

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aggressive (uh-GREH-siv)

In medicine, describes a tumor or disease that forms, grows, or spreads quickly. It may also describe treatment that is more severe or intense than usual.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

antigen (AN-tih-jen)

Any substance that causes the body to make a specific immune response.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

blood (blud)

A tissue with red blood cells, white blood cells, platelets, and other substances suspended in fluid called plasma. Blood takes oxygen and nutrients to the tissues, and carries away wastes.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

cancer (KAN-ser)

A term for diseases in which abnormal cells divide without control and can invade nearby tissues. Cancer cells can also spread to other parts of the body through the blood and lymph systems. There are several main types of cancer. Carcinoma is a cancer that begins in the skin or in tissues that line or cover internal organs. Sarcoma is a cancer that begins in bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue. Leukemia is a cancer that starts in blood-forming tissue such as the bone marrow, and causes large numbers of abnormal blood cells to be produced and enter the blood. Lymphoma and multiple myeloma are cancers that begin in the cells of the immune system. Central nervous system cancers are cancers that begin in the tissues of the brain and spinal cord. Also called malignancy.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

cell (sel)

The individual unit that makes up the tissues of the body. All living things are made up of one or more cells.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

clinical (KLIH-nih-kul)

Having to do with the examination and treatment of patients.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

complete remission (kum-PLEET reh-MIH-shun)

The disappearance of all signs of cancer in response to treatment. This does not always mean the cancer has been cured. Also called complete response.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

complication (kom-plih-KAY-shun)

In medicine, a medical problem that occurs during a disease, or after a procedure or treatment. The complication may be caused by the disease, procedure, or treatment or may be unrelated to them.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

donor (DOH-ner)

In medicine, a person who gives blood, cells, tissue, or an organ for use in another person, such as in a blood transfusion or an organ transplant.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

EBV

A common virus that remains dormant in most people. It causes infectious mononucleosis and has been associated with certain cancers, including Burkitt lymphoma, immunoblastic lymphoma, and nasopharyngeal carcinoma. Also called Epstein-Barr virus.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

Epstein-Barr virus (ep-stine-BAR VY-rus)

A common virus that remains dormant in most people. It causes infectious mononucleosis and has been associated with certain cancers, including Burkitt lymphoma, immunoblastic lymphoma, and nasopharyngeal carcinoma. Also called EBV.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

HLA

One of a group of proteins found on the surface of white blood cells and other cells that play an important part in the body's immune response to foreign substances. These antigens vary from person to person, and HLA tests are done before organ transplantation to find out if tissues match between a donor and a recipient. Also called human leukocyte antigen and human lymphocyte antigen.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

immune system (ih-MYOON SIS-tem)

The complex group of organs and cells that defends the body against infections and other diseases.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

infusion (in-FYOO-zhun)

A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

leukocyte (LOO-koh-site)

A type of immune cell. Most leukocytes are made in the bone marrow and are found in the blood and lymph tissue. Leukocytes help the body fight infections and other diseases. Granulocytes, monocytes, and lymphocytes are leukocytes. Also called WBC and white blood cell.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

liver (LIH-ver)

A large organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

lymph (limf)

The clear fluid that travels through the lymphatic system and carries cells that help fight infections and other diseases. Also called lymphatic fluid.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

lymphoma (lim-FOH-muh)

Cancer that begins in cells of the immune system. There are two basic categories of lymphomas. One kind is Hodgkin lymphoma, which is marked by the presence of a type of cell called the Reed-Sternberg cell. The other category is non-Hodgkin lymphomas, which includes a large, diverse group of cancers of immune system cells. Non-Hodgkin lymphomas can be further divided into cancers that have an indolent (slow-growing) course and those that have an aggressive (fast-growing) course. These subtypes behave and respond to treatment differently. Both Hodgkin and non-Hodgkin lymphomas can occur in children and adults, and prognosis and treatment depend on the stage and the type of cancer.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

malignancy (muh-LIG-nun-see)

A term for diseases in which abnormal cells divide without control and can invade nearby tissues. Malignant cells can also spread to other parts of the body through the blood and lymph systems. There are several main types of malignancy. Carcinoma is a malignancy that begins in the skin or in tissues that line or cover internal organs. Sarcoma is a malignancy that begins in bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue. Leukemia is a malignancy that starts in blood-forming tissue such as the bone marrow, and causes large numbers of abnormal blood cells to be produced and enter the blood. Lymphoma and multiple myeloma are malignancies that begin in the cells of the immune system. Central nervous system cancers are malignancies that begin in the tissues of the brain and spinal cord. Also called cancer.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

oncologist (on-KAH-loh-jist)

A doctor who specializes in treating cancer. Some oncologists specialize in a particular type of cancer treatment. For example, a radiation oncologist specializes in treating cancer with radiation.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

oncology (on-KAH-loh-jee)

The study of cancer.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

organ (OR-gun)

A part of the body that performs a specific function. For example, the heart is an organ.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

partial remission (PAR-shul reh-MIH-shun)

A decrease in the size of a tumor, or in the extent of cancer in the body, in response to treatment. Also called partial response.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

pediatric (pee-dee-A-trik)

Having to do with children.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

recipient (reh-SIH-pee-ent)

In medicine, a person who receives blood, cells, tissue, or an organ from another person, such as in a blood transfusion or an organ transplant.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

spleen (spleen)

An organ that is part of the lymphatic system. The spleen makes lymphocytes, filters the blood, stores blood cells, and destroys old blood cells. It is located on the left side of the abdomen near the stomach.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

stable disease (STAY-bul dih-ZEEZ)

Cancer that is neither decreasing nor increasing in extent or severity.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

stem cell (stem sel)

A cell from which other types of cells develop. For example, blood cells develop from blood-forming stem cells.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

therapeutic (THAYR-uh-PYOO-tik)

Having to do with treating disease and helping healing take place.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

therapy (THAYR-uh-pee)

Treatment.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

tissue (TIH-shoo)

A group or layer of cells that work together to perform a specific function.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

transplantation (tranz-plan-TAY-shun)

A surgical procedure in which tissue or an organ is transferred from one area of a person’s body to another area, or from one person (the donor) to another person (the recipient).

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

trigger (TRIH-ger)

In medicine, a specific event that starts a process or that causes a particular outcome. For example, chemotherapy, painful treatments, or the smells, sounds, and sights that go with them may trigger anxiety and fear in a patient who has cancer. In allergies, exposure to mold, pollen or dust may trigger sneezing, watery eyes, and coughing.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

virus (VY-rus)

In medicine, a very simple microorganism that infects cells and may cause disease. Because viruses can multiply only inside infected cells, they are not considered to be alive.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)

will (wil)

A legal document in which a person states what is to be done with his or her property after death, who is to carry out the terms of the will, and who is to care for any minor children.

Source: The National Cancer Institute's Dictionary of Cancer Terms(http://www.cancer.gov/dictionary)